AB0300 GENETIC EVIDENCE REVEALS A CAUSAL RELATIONSHIP BETWEEN RHEUMATOID ARTHRITIS AND INTERSTITIAL LUNG DISEASE
Authors: Y. W. Zhang, R. Zhao, J. C. Guo, J. Y. Yao, S. X. Zhang, X. Li, C. Wang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The most common extra-articular manifestation of rheumatoid arthritis (RA) is interstitial lung disease (ILD)<sup>[1]</sup> which in severe cases can lead to a range of complications and is one of the leading causes of death in patients with RA<sup>[2]</sup>. Many genetic studies found that patients with RA demonstrated an excess of mutations in genes that have been previously linked to ILD like TERT and RTEL1 et al. However, there is no directly evidence that the two diseases are causally related. <h3>Objectives</h3> In this paper, bidirectional two-sample Mendelian method was used to focus on the genetic factors related to ILD and RA, and to explore the causal relationship between ILD and RA in the pathogenesis. <h3>Methods</h3> A two-sample bi-directional Mendelian randomization (MR) approach was conducted to investigate the causal relationships between RA and ILD. Summary statistics for RA (14,361 RA cases and 43,923 healthy controls (HCs)) and ILD (1,969 cases and 196,986 HCs) were obtained from an available meta-analysis of published genome-wide association studies (GWAS). Relevant single nucleotide polymorphisms (SNPs) were selected by executing quality control steps (p &lt; 1.0 × 10<sup>-5</sup>) from the GWAS summary results. MR analyses progressed mainly using inverse variance weighted (IVW), weighted median (WM), and MR-Egger regression methods. For assessing the robustness of the results, we also carried out sensitivity analysis to assess heterogeneity and pleiotropy, such as MR-Egger, leave-one-out and MR pleiotropy residual sum and outlier (MR-PRESSO). <h3>Results</h3> Our study discovered a bidirectional causal effect between RA and ILD. The presence of ILD may increase the risk of RA by 12.8% (OR: 1.128, 95%CI: 1.013-1.256, P = 0.029). Similarly, the existence of RA may increase the risk of ILD by 9.4% In addition, reverse MR analysis found that RA also influenced the risk of ILD significantly (OR: 1.094, 95%CI: 1.023-1.171, P = 0.009). Sensitivity analysis showed no pleiotropy but have heterogeneity (Q = 0.030) in reverse MR analysis. <h3>Conclusion</h3> MR analysis supported a potential causal relationship between RA and ILD. In RA and ILD, no matter which disease the patient has, it will greatly increase the risk of another disease. This study increases the emphasis on therapeutic or defensive interventions for patients with RA or ILD in the future to reduce severe complication and mortality. <h3>References</h3> [1] Kadura S, Raghu G. Rheumatoid arthritis-interstitial lung disease: manifestations and current concepts in pathogenesis and management. Eur Respir Rev 2021;30(160) doi: 10.1183/16000617.0011-2021 [published Online First: 2021/06/26] [2] England BR, Hershberger D. Management issues in rheumatoid arthritis-associated interstitial lung disease. Curr Opin Rheumatol 2020;32(3):255-63. doi: 10.1097/bor.0000000000000703 [published Online First: 2020/03/07] <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.